Folic Acid Modified Polymeric Micelles for Intravesical Instilled Chemotherapy

摘要

In this study, a targeting micellar drug delivery system was developed for intravesical instilled chemotherapy of bladder cancer. The amphiphilic diblock copolymer poly(?-caprolactone)-block-poly(ethylene glycol)(PCL-b-PEO) with functional amino group(NH2) at the end of PEO block was synthesized. Then the copolymer was conjugated with folic acid(FA) and fluorescein isothiocyannate(FITC) via the PEO-NH2 terminus, and then assembled into micelles with the target moiety and fluorescence labeling. In addition, drug loaded micelles were also fabricated with anticancer drug doxorubicin(DOX) encapsulated in the hydrophobic core. The micelles were characterized in terms of size, drug loaded efficiency and critical micellization concentration(CMC) by means of DLS, UV and fluorescence spectra. In vitro cellular uptake and cytotoxicity studies showed that FA modified PCL-b-PEO-FA micelles have a greater targeting efficiency to human bladder cancer cell(T-24 cell) compared to PCL-b-PEO-NH2 micelles due to the conjugation of FA on the surface, while no targeting effect to normal tissue originated human embryonic kidney 293(HEK-293) cells was observed, enabling the micelles a promising drug carrier for intravesical instilled chemotherapy of bladder cancer.